The administration of vitamin A to pregnant mice produces facial and limb malformations which resemble some of those observed in certain human syndromes. The purpose of this project is to determine the cellular and biochemical mechanism by which vitamin A causes malformations. The results indicate that the vitamin A induced malformations are due to an inhibition of neural crest cell migration and the inhibition of chondrogenesis. Studies, using developing limb bud cell cultures, showed that vitamin A causes contact inhibition and increased cell-cell adhesion suggesting cell surface changes. Cell surface labeling studies indicate that vitamin A treatment increases the accumulation of a 220,000 dalton cell surface glycoprotein.